This is an application for a Mentored Patient-Oriented Research Career Development Award (K23). The candidate is a geriatric psychiatrist who proposes to acquire the specific skills and knowledge necessary to become an independent investigator and leader in geriatric depression treatment research. Among the aged, major depression is a common problem which causes significant morbidity and mortality. While effective treatments exist for major depression, the speed, extent, and permanence of treatment response are unpredictable and vary widely, thus leaving considerable residual symptoms and disability. The candidate proposes to use the tools of functional neuroimaging to examine the underlying biology of treatment response variability in geriatric depression in order to predict and optimize antidepressant treatment response. Career development activities emphasize an integrative approach and focus on treatment research methodology, functional neuroimaging, and geriatric psychopharmacology. The research plan involves a treatment trial for elders with major depression combined with fluorine-18 deoxyglucose positron emission tomography before and after 10 weeks of acute treatment with paroxetine. Reduction in the Hamilton Depression Scale score will be correlated with cerebral metabolism in neuroanatomical regions of interest. It is hypothesized that pretreatment anterior cingulate hypermetabolism will correlate positively with extent of antidepressant response to acute treatment. Possible sources of variance accounting for treatment response heterogeneity (e.g., cerebrovascular disease reflected as white matter hyperintensities on brain magnetic resonance imaging, age of illness onset, and serum paroxetine concentration) will also be examined. As continuation and maintenance treatment will be offered through the Mental Health Clinical Research Center for the Study of Late-Life Mood Disorders, regional cerebral glucose metabolism before and after acute treatment will also be examined with respect to long-term clinical outcome.